High-resolution melting analysis ( HRMA/HRM ), a simple, rapid, flexible, inexpensive closed tube approach with high sensitivity and specificity has been one of the most widely used molecular diagnostic techniques in clinicalas well as in research settings .Recently, rapid development ofinstruments , DNA dyes and analysis software significantly enhance the sensitivity , specificity and accuracy of HRM,providing a fast, efficient and economic molecular diagnostic platform for molecular diagnosis of inherited disease , molecular profiling and target therapy of cancer , identification of pathogen , as well as individualized medicine.

Objective To study the clinical effect of expert tibial nail (ETN) in the treatment of distal tibial fractures. Methods From October 2007 to June 2008,ETN was performed in 13 patients with distal tibial fractures. There were eight males and five females, at age range of 25-47 years (33.8 on average). According to AO/ASIF classification, there were three patients with 43-A1 fractures, four with 43-B1 fractures, four with 43-B2 fractures and two with 43-C1 fractures. All the patients were with close fractures except for three patients with Gustilo-Anderson type Ⅰ fractures. Their clinical data were analyzed for assessing the clinical effect of ETN. Results All patients were followed up for a mean time of 8.4 months (range 3-13 months), which showed that all the fractures obtained stable fixation and sound healing, with no complications like breakage of ETN, wound infection, fracture nonunion or limb shortening. According to Johner-Wruhs standard, the functional results were excellent in 10 patients and good in three. Conclusion ETN has advantages of minimal invasion, shorter operation time, stronger fixation,better soft tissue protection and better functional recovery for distal tibial fractures in comparison with traditional open reduction and buttress plate fixation.

Objective To evaluate preliminary effect of In-Space percataneous interspinous spacer in the treatment of lumbar instability.Methods Data of 18 patients who had undergone interspinous spacer implant for lumbar instability from May 2009 to June 2011 were retrospectively analyzed.There were 10 males and 8 female,aged from 39 to 58 years.All patients suffered from varying degrees of lower back pain induced by lumbar hyperextension,as well as radiating and segmental pain of unilateral lower limb.The visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate clinical outcomes.The pre-and postoperative interspinous distance,trailing edge height of intervertebral space,foraminal width,foraminal height,segmental lordotic angle and lumbar range of motion were tested and compared.Results All patients were followed up for 18 to 36 months.The VAS score improved from preoperative 7.9±2.1 to 3.1±1.3 at 6 months postoperatively and 1.5±0.8 at final follow-up.The ODI improved from preoperative 82.1％±13.1％ to 54.7％±14.8％ at 6 months postoperatively and 10.1％±2.5％ at final follow-up.The postoperative interspinous distance,trailing edge height of intervertebral space,foraminal height,foraminal width,segmental lordotic angle and lumbar range of motion were 9.29±1.43 mm,11.28±0.85 mm,21.27±1.01 mm,10.83±0.73 mm,7.62°±0.74° and 6.34°±0.81°,respectively.Wound healed smoothly in all patients,and there were no complications such as spinous process fracture,spinal cord injury,cerebrospinal fluid leakage,device displacement and device dislocation.Conclusion It is easy and safe to use In-Space percataneousinterspinous spacer in the treatment of lumbar instability,and the preliminary effect is satisfactory.

The ubiquitin-proteasome pathway is responsible for the degradation of most cellular proteins in eukaryotes.It regulates almost all cellular activities, including cell proliferation, differentiation, apoptosis, gene transcription, and DNA repair.The dysfunction of the ubiquitin-proteasome pathway is associated with the pathogenesis of numerous human diseases, including cancer and neurodegenerative diseases.The marketed proteasome inhibitors have been successfully used to treat multiple myeloma and mantle cell lymphoma.Furthermore, novel inhibitors against the components of the ubiquitin-proteasome pathway are under developed and exhibit promising therapeutic effects in vivo.This paper will briefly introduce the progress on the drug discovery related to the ubiquitin-proteasome pathway.

Objective:To investigate the feasibility and safety of fetal intravascular transfusion via the intrahepatic vein in the treatment of fetal anemia.Methods:This was a retrospective analysis of all fetuses requiring intrauterine transfusion (IUT) in the Shanghai First Maternity and Infant Hospital between January 2010 and December 2019. According to the different ways of IUT, they were divided into intrahepatic venous transfusion group and umbilical venous transfusion group, fetal outcomes and the incidence of procedure-related complications between the two groups were compared.Results:A total of 97 IUTs were performed on 48 fetuses. Among them, 16 cases were performed in the intrahepatic vein (31 transfusions), 32 cases were performed in the cord of the umbilical vein (66 transfusions).There were no significant differences between the two groups in age, labor history and the proportion of fetal hydrops before the first transfusion. In the intrahepatic venous transfusion group, the posterior placenta was 14/16, which was significantly higher than 78% (25/32) in the umbilical venous transfusion group ( P<0.01). The live-birth rates of the two groups were 13/16 and 75% (24/32). There was no significant difference between the two groups ( P>0.05). Before intrahepatic venous transfusion, the proportion of fetal hydrops was significantly higher than that of umbilical venous transfusion [55% (17/31) vs 24% (16/66), P<0.05]. Puncture success rate of intrahepatic venous transfusion and umbilical venous transfusion were both 100%. In the umbilical venous transfasion group, the incidence of needle slippage (5%, 3/66) and the abnormality of fetal heart rate (11%, 7/66) were higher than those in the intrahepatic venous transfasion group [0 and 3% (1/31)], but there were no significant differences between the two groups (all P>0.05). There were no cases of fetal loss within 24 hours, premature rupture of membranes, infection within 7 days and emergency cesarean section after IUT in both groups. Conclusions:Fetal intravascular transfusion via the intrahepatic vein is safe and feasible in the treatment of fetal anemia. But the requirements of puncture technique are relatively high, so it is recommended to be carried out in experienced fetal treatment center.

To assess the perinatal outcomes following selective feticide through radiofrequency ablation (RFA) in complex monochorionic pregnancies. Methods In this retrospective observational study, 34 cases of complex monochorionic pregnancies treated with RFA for selective feticide and delivered at the Shanghai First Maternity and Infant Hospital between January 1, 2012 and December 31, 2013, were included. Gestational age at RFA, the number of RFA cycles, maternal and fetal complications, gestational age at delivery, neonatal outcomes at 28 days after birth and neonatal development after birth were recorded. Fetal survival rate were defined as the number of survivors at 28 days after birth divided by the number of remaining fetuses after RFA. Factors affecting fetal survival rate were also analyzed. Statistical analysis was performed using Fisher's exact test. Results (1) The process for RFA:The gestatinal age for the procedure was (20.7±3.1) weeks(16+1-27+6 weeks). The successful rate of procedures was 100%(34/34) and the cycle number for RFA was 1-6 times. (2)Fetal complications and survival rate of remaining fetuses after RFA:there were six pregnant women suffering from premature rupture of membrane (PROM) before 28 weeks. Among those women, one had miscarriaged at 25 weeks, one chose to terminate at 26 weeks and the remaining four chose to continue the pregnancy. There were three remaining fetuses developing fetal severe anemia with hydrops after RFA. Two of them had fetal demises 2 days after the procedures and one chose to have termination. Another two cases with discordant fetal anomalies had fetal demises with unknown reasons one day after RFA. There were 27 remaining fetuses after RFA who survived until 28 days after birth. The mean gestational age at delivery was(36.4±4.1)weeks (26+4-40 weeks) and the mean birth weight was (2 913± 978) g (1 080-4 600 g). The overall fetal survival rate 28 days after birth was 79%(27/34). There were no abnormal findings in antenatal magnetic resonance imaging (MRI) four weeks after the procedure and no abnormal development of nervous system in the surviving neonates between 3 months old and 1.5 years old. (3) Factors affecting fetal survival rate :There were no significant differences identified in the rate of fetal severe anemia and fetal demise (2/15, 2/13 and 1/6), the rate of PROM before 28 weeks (1/15, 4/13 and 1/6) and survival rate of 28 days after birth (13/15, 10/13 and 4/6)among three groups with different gestational age (16+1-, 20- and 24-27+6 weeks) for RFA(all P>0.05). The indications for RFA included severe selective intrauterine growth restriction (50%, 17/34), discordant for fetal abnormalities(24%, 8/34) , twin reversed arterial perfusion sequence(18%, 6/34)and dichorionic or monochorionic triamniotic pregnancy (9%, 3/34). There were also no significant differences noted in the rate of fetal complications and fetal demise(3/17, 2/8, 0/6, 0/3), the rate of PROM before 28 weeks (3/17, 0/8, 2/6, 1/3)and survival rate of 28 days after birth among different groups (12/17, 6/8, 6/6, 3/3) with different indications for RFA(all P>0.05) . No significant differences observed in the rate of fetal complications and fetal demise(10% and 2/5)and the rate of PROM before 28 weeks (17%and 2/5)between two groups with different cycle numbers for RFA (<3 times and≥3 times, all P<0.05), while the group with cycle number ≥ 3 times had lower survival rate 28 days after birth than the group with cycle number<3 times for RFA (2/5 vs 86%, P<0.05). Conclusions RFA is one of effective and safe procedures for selective feticide in complex monochorionic pregnancies.

Objective To review the diagnosis,monitoring,management and perinatal outcomes of monochorionic monoamniotic (MCMA) twin pregnancy.Methods From July 2010 to August 2013,there were 17 MCMA twin pregnancies diagnosed and delivered in Shanghai First Maternity and Infant Hospital.According to the MCMA management protocol,induced abortion,elective fetal reduction,and anticipant pregnancy were optional.For those anticipant pregnancies,fetal lung underwent maturation promotion at gestational weeks 28; hospitalization with 40 min/day continual fetal electronic monitoring and umbilical blood monitoring twice weekly at gestational weeks 28-30; 40 min continual fetal electronic monitoring twice daily and umbilical blood monitoring once every other day at gestational weeks 30-32; and 40 min continual fetal electronic monitoring three times daily and umbilical blood monitoring once daily at gestational weeks 32-34; and pregnancy ended on time.The presence of umbilical cord entanglement,congenital malformation,intrauterine fetal death,complications exclusive to monochorionic twins (e.g.selective fetal growth restriction,twin reversed arterial perfusion sequence and twin-twin transfusion syndrome) and the perinatal outcomes were retrospectively analyzed.Results Average maternal age of women with 17 MCMA twins was (29.0±2.7) years,and all were primiparas.They were diagnosed at (18.6± 5.5) weeks on average (11 +5-28+1 weeks).Umbilical cord entanglements were detected in all cases by ultrasonography and confirmed postnatally.There were three cases of complications specific to monochorionic twins,including two with selective fetal growth restriction and one with twin reversed arterial perfusion sequence.There were seven women with fetal congenital malformation; four of whom chose induced abortion; one case of anencephaly chose radiofrequency ablation fetal reduction,and the remaining two cases with congenital malformation and ten cases without chose anticipant pregnancy,and there were no abnormal ultrasonography signs during pregnancy.Among these 12 cases,intrauterine fetal death of both fetuses occurred in two cases at 16 and 21+1 weeks gestation and they were aborted.Intrauterine fetal death of a single fetus occurred in one case at 30+2 weeks gestation (another fetus was delivered by emergency cesarean section).There were a total of eleven live births delivered by cesarean section (four by emergency cesarean section) at a median gestational age of (32.7± 1.6) weeks.There were 20 live neonates with a mean birth weight of (1 850±496) g.Sixteen neonates were transferred to the neonatal intensive care unit and hospitalized for (37.9± 16.4) days.Nine neonates suffered from respiratory distress syndrome but were eventually cured.Conclusions MCMA twin pregnancy has high morbidity and mortality.Early ultrasonography helps to clarify the diagnosis and enhance the monitoring,thus improving the perinatal outcomes.

Objective To investigate the association between placental sharing,vascular anastomoses,cord insertion and perinatal outcome in uncomplicated monochorionic diamniotic (MCDA) placentas.Methods Between January 1,2012 and July 31,2013,60 uncomplicated (seclective fetal growth restriction,twin anemia-polycythemia sequence and twin-twin transfusion dyndrome) MCDA placentas were studied.These uncomplicated MCDA placentas were divided into the placenta equally shared group with placental territory discordance (PTD) ＜0.25 and the placenta unequally shared group with PTD ≥ 0.25.Angioarchitecture,cord insertion type and the distance between two cord insertions were compared using the Chi-square test and nonparametric test.Results Mean maternal age was (30.3±4.1) years.There were 39 cases (65％) in the placenta equally shared group and 21 (35％) in the placenta unequally shared group.Vascular anastomoses were observed in all placentas,arterioarterial anastomoses in 58 placentas (97％),and venovenous anastomoses in 17 placentas (28％).The overall diameter and the maximum diameter of arterioarterial anastomoses in the placenta equally shared group were (0.19±0.11) cm and (0.18±0.09) cm,respectively,and were lower than those in the placenta unequally shared group [(0.27±0.11) cm and (0.27±0.12) cm,respectively] (T were-2.39 and-2.94,P＜0.05,respectively).No significant differences in the number,the overall diameter and the maximum diameter of venovenous anastomoses were observed between the two groups (all P＞0.05).The incidence of cord velamentous insertion and cord velamentous insertion plus cord marginal insertion were 14％ (11/78) and 42％ (33/78),respectively,in the placenta equally shared group,and were similar to those in the placenta unequally shared group [14％ (6/42) and 33％ (14/42),x2 were 1.00 and 0.43,P＞0.05,respectively].The mean distance between two cord insertions was shorter in the placenta unequally shared group than in the placenta equally shared group [(14.3±6.3) cm vs (18.2±6.0) cm,T=2.37,P＜0.05].Conclusions In cases with unequally shared placenta,the distance between two cord insertions is shorter and the diameter of arterioarterial anastomoses is larger,which may compensate for their unequal placental territories,leading to no complications in these MCDA twin.

Objective To investigate the difference of short-term clinical efficacy between decompressive laminectomy into In-Space and simple decompressive laminectomy for treatment of lumbar spinal stenosis with vertebral instability.Methods Thirty-three patients with lumbar spinal stenosis with vertebral instability admired from May 2009 to July 2010,were divided into two groups by random number table.Group A of 16 cases was treated with laminectomy decompression and placement In-Space,group B of 17 cases was treated with laminectomy decompression.Lumbar anteroposterior,lateral and flexion-extension X-ray films,preoperatively,and the follow-up were used to measure anterior and posterior disc height,foraminal height,segmental lordotic angle at surgical level.Using Oswestry disability index (ODI) and the visual analogue scale (VAS) to evaluate the clinical efficacy.Results All patients were followed up for (13.20 ± 2.91 ) months (range 6 to 21 months).The anterior disc height after operation of group A was slightly decreased compared with the preoperative(P＞ 0.05 ),the posterior disc height at 1 day after operation and foraminal height after operation of group A were significantly increased compared with the preoperative (P＜ 0.05).The anterior and posterior disc height,foraminal height of group B at 1 day,1 month,3 months after operation were no significantly different compared with the preoperative (P ＞ 0.05 ),at 6 months after operation and the end of follow-up were significantly decreased compared with the preoperative or 1 day after operation (P ＜ 0.05 ).Activity of lumbar vertebra by preoperative 9.86° ± 1.90° decreased to the end of followup 5.60° ± 2.02°in group A,while activity of lumbar vertebra by preoperative 9.89° ± 2.00°increased to the end of follow-up 10.76° ± 3.14° in group B.At the end of follow-up,lumbar back pain VAS,ODI score [ (2.02 ± 1.98 ),( 20.18 ± 18.80) scores ] of group A were significantly lower than those of group B [ (4.15 ±2.36),(30.39 ± 16.62 ) scores ],the differences were statistically significant (P ＜ 0.05 ).No patient suffered In-Space loosening,fracture and emerge.Conclusion The operation of In-Space can maintain spinal mobility and stability as well as avoiding lumbar vertebral instability,and its short-term efficacy is satisfactory.

Objective To explore a new mode of prenatal diagnosis and counseling for congenital heart disease (CHD) by interdisciplinary cooperation and the value of Grading scale of fetal echocardiography in disease management.Methods The Grading scale of fetal echocardiography and a new integrative service mode of prenatal diagnosis and counseling for CHD with multidisciplinary team,including obstetric sonographers,obstetricians,pediatric cardiologists and geneticists,was established.For pregnant women referred to prenatal clinic in Shanghai First Maternity and Infant Hospital from January 1,2011 to December 31,2012,counseling about the diagnosis,severity,treatment options and long-term prognosis would be provided based on detailed fetal echocardiography and the grading scales.The significance of such mode in the prenatal management of CHD was analyzed and the rate of pregnancy termination was compared by Fisher exact test.Result According to the Grading scale of fetal echocardiography,there were four categories:Class Ⅰ,minor anomalies probably without treatment requried; Class Ⅱ,simple defects with normal life quality following after-born therapy; Class Ⅲ,complex anomalies with reasonable life quality after treatment; Class Ⅳ,severe malformation requiring multiple stage surgical repair or with very poor prognosis.There were a total of 54 pregnancies confirmed to have fetal cardiac anomalies by echocardiography,among which 27 were terminated.The average age of pregnant women was (29±3) years old,the average gestational week was 28.0±3.8.The abortion rate in women with the fetuses diagnosed as Class Ⅳ CHD was 17/19,higher than that in Class Ⅰ,Ⅱ and Ⅲ (3/15,3/10 and 4/10,Fisher exact test,all P＜0.01).In 19 Class Ⅳ cases,only two twin pregnant women continued their pregnancies because the other fetuses were healthy.Abortion was conducted in all 7 fetuses associated with extra-cardiac,chromosome anomaly or genetic syndrome.Conclusion The establishment of new integrated mode of prenatal diagnosis and counseling for CHD and Grading scale of fetal echocardiography in a multidisciplinary manner could provide comprehensive and authentic information and ethical advices for the families.